N,N'-Dicyclohexylurea → 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]ethanone

HRID 2357443Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2357443
ON1C2C=CC=CC=2N=N1.[NH:11]1[CH2:15][CH2:14][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[CH2:12]1.CN1CCOCC1.[CH3:32][N:33]([CH3:50])[C:34]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:39][CH2:38][C:37](=[CH:40][C:41](O)=[O:42])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O.[OH-].[Na+]>CN(C)C=O.O>[CH3:50][N:33]([CH3:32])[C:34]1([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:39][CH2:38][C:37](=[CH:40][C:41]([N:11]2[CH2:15][CH2:14][CH:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH2:12]2)=[O:42])[CH2:36][CH2:35]1

Komponenten

10

Edukt 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 184096763-(pyrrolidin-3-yl)-1H-indoleHCID 574382874-Dimethylamino-4-phenylcyclohexylidene-acetic acid

Produkt 1

HCID 104571352-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]ethanoneAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-hydroxybenzotriazole (810 mg, 6.0 mmole), 3-pyrrolidine-3-yl-1H-indole (558 mg, 3.0 mmole) and N-methylmorpholine (0.666 ml, 6.0 ml) were added in succession to a solution of 4-dimethylamino-4-phenylcyclohexylidene-acetic acid (891 mg, 3.0 mmole) in dry dimethylformamide (15 ml) under argon. The solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.2 g, 6.0 mmole) was added. The reaction mixture was stirred for 4 days at RT, the dicyclohexylurea precipitating out little by little. The reaction mixture was worked up by separating the precipitated urea and adding the filtrate to a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Further urea thereby precipitated out, which was separated. The aqueous phase was diluted with water (300 ml), 5M sodium hydroxide (7 ml, 35 mmole) was added, and the whole was kept for three days at 5° C. The crude product consisting of the amide precipitated out as a beige-coloured solid (994 mg). After chromatographic separation on silica gel (80 g) with EE/methanol (1:1), 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]ethanone was isolated as a colourless solid with an m.p. of 94°-97° C. in a yield of 46% (585 mg). The compound was obtained as a diastereoisomer mixture.

Aufarbeitung

  1. temperatureThe solution was cooled in an ice bath
  2. customby separating the precipitated urea
  3. additionadding the filtrate
  4. additionto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customFurther urea thereby precipitated out
  6. customwhich was separated
  7. additionwas added
  8. waitthe whole was kept for three days at 5° C
  9. customprecipitated out as a beige-coloured solid (994 mg)
  10. customAfter chromatographic separation on silica gel (80 g) with EE/methanol (1:1)

Quellen und Nachweise

ORD-Eintrag
ord-1ba7bba0d5a94ab787dab2cea406e640
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759385B2

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